Pain
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A recently defined structure, the rostromedial tegmental nucleus (RMTg; aka tail of the ventral tegmental area [VTA]), has been proposed as an inhibitory control center for dopaminergic activity of the VTA. This region is composed of GABAergic cells that send afferent projections to the ventral midbrain and synapse onto dopaminergic cells in the VTA and substantia nigra. These cells exhibit µ-opioid receptor immunoreactivity, and in vivo, ex vivo, and optogenetic/electrophysiological approaches demonstrate that morphine excites dopamine neurons by targeting receptors on GABAergic neurons localized in the RMTg. ⋯ Our data show that locally infused RMTg morphine or selective RMTg GABAergic neuron inhibition produces 87% of the maximal antinociceptive effect of systemic morphine, and RMTg GABAergic neurons modulate dopamine release in the nucleus accumbens. In addition, chemoactivation of VTA dopamine neurons significantly reduced pain behaviors both in resting and facilitated pain states and reduced by 75% the dose of systemic morphine required to produce maximal antinociception. These results provide compelling evidence that RMTg GABAergic neurons are involved in processing of nociceptive information and are important mediators of opioid analgesia.
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Compression of the trigeminal root entry zone by a blood vessel can cause trigeminal neuralgia (TN). However, a neurovascular conflict does not explain all cases of TN, and TN can exist without a neurovascular contact. A common observation during microvascular decompression surgery to treat TN is arachnoiditis in the region of the trigeminal nerve. ⋯ The main finding was that immunological protein levels in the cerebrospinal fluid from patients with TN decreased after surgery towards levels observed in healthy controls. Two proteins seemed to be of specific interest for TN: TRAIL and TNF-β. Thus, inflammatory activity might be one important mechanism in TN.
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There is evidence of greater opioid prescription to individuals in the United States with mental health conditions. Whether these associations generalize beyond the US prescription environment and to familial mental health and socioeconomic status (SES) has not been examined comprehensively. This study estimated associations of diverse preexisting mental health diagnoses, parental mental health history, and SES in childhood with opioid analgesic prescription patterns nationwide in Sweden. ⋯ All mental health conditions were associated with greater LTOT rates (hazard ratios from 1.66 [1.56-1.77] for bipolar disorder to 3.82 [3.51-4.15] for opioid use disorder) and were similarly associated with concurrent benzodiazepine-opioid therapy. Among 1,482,462 adolescents and young adults, initiation and LTOT rates were greater for those with parental mental health history or lower childhood SES. Efforts to understand and ameliorate potential adverse effects of opioid analgesics must account for these patterns.
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Randomized Controlled Trial
Repetitive transcranial magnetic stimulation of the primary motor cortex expedites recovery in the transition from acute to sustained experimental pain: a randomised, controlled study.
Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) is increasingly being investigated as a means of alleviating chronic pain. However, rTMS interventions are typically initiated once pain has already become chronic and maladaptive patterns of neural activity are likely to have been established. A critical question is whether M1 rTMS applied soon after pain onset can prevent the development of maladaptive neural activity and promote recovery. ⋯ Corticomotor excitability and descending inhibitory pain control did not differ between groups. These findings suggest that active excitatory M1 rTMS promotes recovery of muscle soreness, pain, and mechanical hyperalgesia in the transition from acute to sustained experimental pain. The analgesic effects of M1 rTMS do not seem to be modulated by descending inhibitory pain control or local changes in corticomotor excitability.
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Pain is a dynamic experience subject to substantial individual differences. Intensive longitudinal designs best capture the dynamical ebb and flow of the pain experience across time and settings. Thanks to the development of innovative and efficient data collection technologies, conducting an intensive longitudinal pain study has become increasingly feasible. ⋯ Finally, we provide statistical software syntax for calculating the aforementioned intraindividual pain variability indices so that researchers can easily apply them in their research. We believe that investigating intraindividual variability of pain will provide a new perspective for understanding the complex mechanisms underlying pain coping and adjustment, as well as for enhancing efforts in precision pain medicine. Audio accompanying this abstract is available online as supplemental digital content at http://links.lww.com/PAIN/A817.